This is a continuation of a long-term project designed to gain fundamental information about the mechanisms of action of purine and pyrimidine analogs and about the enzymes with which these analogs or their derivatives interact: 1. Studies on the pathways of polyphosphate nucleotide synthesis and degradation. The enzymes currently under study include nucleoside diphosphokinase which is markedly heterogeneous in human erythrocytes. Three isozymes have been purified and comparative studies are under way. Human erythrocytic adenosine deaminase has been purified and the effects of nucleoside analogs as inhibitors and substrates are being studied. 2. Studies on the mechanism of cytolytic action of purine and purine ribonucleoside analogs. Methods have been developed for the direct detection of analog nucleotides such as 6-thioIMP, 6-selenoGMP, 6-thioGTP, etc., in tissue extracts. The incorporation of large quantities of analog nucleotides into human erythrocytes has been observed as well as the interchange between the mono-, di- and triphosphate nucleotide pools. 3. Collaborative studies on schistosomiasis in collaboration with the laboratory of A.W. Senft. Studies of purine metabolism in Schistosoma mansoni are under study, as well as examinations of the incorporation of purine analogs into nucleotide pools. The chemotherapeutic approach of feeding adult schistosomes erythrocytes loaded with purine analogs is being developed.